Induction of Liver Size Reduction in Zebrafish Larvae by the Emerging Synthetic Cannabinoid 4F-MDMB-BINACA and Its Impact on Drug Metabolism

Zebrafish (ZF; Danio rerio) larvae have become a popular in vivo model in drug metabolism studies. Here, we investigated the metabolism of methyl 2-[1-(4-fluorobutyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoate (4F-MDMB-BINACA) in ZF larvae after direct administration of the cannabinoid via microinjection, and we visualized the spatial distributions of the parent compound and its metabolites by mass spectrometry imaging (MSI). Furthermore, using genetically modified ZF larvae, the role of cannabinoid receptor type 1 (CB1) and type 2 (CB2) on drug metabolism was studied. Receptor-deficient ZF mutant larvae were created using morpholino oligonucleotides (MOs), and CB2-deficiency had a critical impact on liver development of ZF larva, leading to a significant reduction of liver size. A similar phenotype was observed when treating wild-type ZF larvae with 4F-MDMB-BINACA. Thus, we reasoned that the cannabinoid-induced impaired liver development might also influence its metabolic function. Studying the metabolism of two synthetic cannabinoids, 4F-MDMB-BINACA and methyl 2-(1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7′N-5F-ADB), revealed important insights into the in vivo metabolism of these compounds and the role of cannabinoid receptor binding.     

Gelation Studies: Comparison of the Critical Exponents Obtained by Dynamic Light Scattering and Rheology, 2

Summary: The sol–gel transition of two thermoreversible gelling mixtures made of xanthan gum and locust‐bean gum has been studied by using in situ, time‐resolved dynamic light scattering (DLS) and in situ rheology. A critical dynamical behavior was observed near the sol–gel transition, which was characterized by the presence of power‐law spectra over three and four decades in the time‐intensity correlation function g₂(t) − 1 ∼ t^−μ and over four and three decades in the oscillatory shear experiment G′(ω) ∼ G″(ω) ∼ ωⁿ. A comparison of the critical exponents obtained (μ₁ ≈ 0.36, μ₂ ≈ 0.32 and n₁ ≈ 0.62, n₂ ≈ 0.67) was made as a function of the dependence of the two mixing ratios according to the theory by Doi and Onuki. New experiments were also performed to compare the critical exponents on such a thermoreversible system.

Double‐logarithmic plot of the time‐intensity correlation functions g₂(t) − 1 versus the delay time, t, at a 90° scattering angle and at several temperatures of the mixture 1.     

Binders for exterior coatings exhibiting low soiling tendency

Elastomeric coatings protect building facades and flat roofs from moisture and weather exposure. As a drawback, these coatings are prone to dirt-pickup due to the low glass transition temperature of the used polymeric binders. Strategies to overcome this enhanced soiling tendency are discussed, and the results of laboratory and outdoor soiling tests are compared. A novel method for the assessment of wet soiling tendency is presented.     

Crystal Structure and Electron Density Distribution in Niobium Carbide

In this paper the bonding properties, e. g. the charge distribution between the atoms and the deformation of niobium carbide densities have been studied. The crystal studied had the composition NbC_0.98. Careful and redundant data collection (74 unique reflections out of 2087 reflections measured) gave the basis for a detailed study. IAM models (independent atom model), high order and multipole refinements were made resulting in R values of R = 0.4% and R = 0.07%. In the corresponding deformation density maps electron accumulations between the niobium atoms were detected, but no bonding to the carbon atoms.     

Thermal Behaviour of Poly(propylene) Layered Silicate Nanocomposites

The thermal degradation behaviour of nanocomposites based upon poly(propylene)/organoclay, modified with protonated octadecyl amine (C18) in comparison to that of non‐exfoliated microcomposites based upon organoclay, modified with protonated butyl amine (C4), was studied by thermogravimetry. In the case of the nanocomposite, the temperature at which volatilisation occurs increases as compared of the microcomposite. Moreover, the thermal oxidation process of the polymer is strongly slowed down in the nanocomposite with high char yield both by a physical barrier effect, enhanced by ablative reassembling of the silicate, and by a chemical catalytic action due to the silicate and to the strongly acid sites created by thermal decomposition of the protonated amine silicate modifier.     

Über die Herstellung transzendenter Funktionen als Grenzwerte rationaler Funktionen

Ohne Zusammenfassung Professor Dr.Anders Wiman zum fünfundsechzigsten Geburtstage gewidmet.